(CNN) The kaleidoscope of Syria's multi-sided war is changing daily and the latest casualty is hope of a US-Russia agreement that would bring about a truce and humanitarian relief.

US Secretary of State John Kerry and his Russian counterpart Sergey Lavrov have been working for three months to negotiate a deal. But ultimately were hampered by "gaps of trust" between the two nations, according to US President Barack Obama.

While it remains unclear exactly what these "gaps of trust" are, they have been at odds about which groups in Syria should be deemed terrorists and which are legitimate factions. President Obama said the US had "grave differences with the Russians in terms of both the parties we support but also the process that is required to bring about peace in Syria."

Too many cooks

Only ISIS is on everyone's blacklist, and it's had another hard week, following the death of one of its most prominent figures at the end of August.

The Turkish military, along with several factions of the Free Syrian Army that it supports, has driven ISIS from twenty or so villages it held along the Syrian border, a strip of land that gave the group critical access to the outside world. At the same time, Turkish intervention has ensured that the Syrian Kurds won't be able to link areas under their control. Now an uneasy stand-off exists between the groups supported by Turkey and Kurdish militia along a broad, ragged front.

The last city of any size in Syria that ISIS holds -- Raqqa -- is under growing pressure, with US and coalition air power carrying out daily airstrikes against ISIS positions.

To the west, the Syrian Army appears to have wiped out the gains made two weeks ago around the city of Aleppo by a collection of Islamist rebel groups. Led by the former al Qaeda affiliate, now rebranded as Jabhat Fateh al-Sham , the rebels had punched through a corridor to besieged parts of the city. But aided by Russian airstrikes and the Hezbollah militia on the ground, Syrian forces have regained control, essentially re-imposing the siege of Aleppo.

These gains and losses go a long way to explaining the absence of diplomatic progress. There are so many parties involved. And most of them -- along with their different sponsors (Russia, Iran, Iraq, Turkey, Saudi Arabia and the Gulf countries, Turkey and the US) -- are still jostling for advantage on the battlefield.

What to do about Bashar al-Assad?

Then there is also the fundamental divide between the US and Russia that hampers any progress: Bashar al-Assad

Russia -- and even more so Iran -- have invested heavily in keeping him in power , especially since last summer, when one defeat after another left the Syrian regime clinging on in many areas.

The US has long said any solution must include Assad's departure. But Moscow appears to have calculated that the US is not going to do much to hasten that event.

Last month White House spokesman Josh Earnest reiterated the Administration's caution.

"We've got a test case just over the border in Iraq about what the consequences are for the United States implementing a regime-change policy and trying to impose a military solution on the situation."

Assad's removal is non-negotiable for a vast number of Syrians, says Aimen Dean, a former jihadist with al Qaeda who subsequently worked for British intelligence. Dean, who has lost two relatives fighting for rebel groups in Syria, quotes an Arab proverb: "I did not fast this long only to break my fast with an onion."

In other words: the only reward that will justify their suffering is Assad's departure and the collapse of his regime.

Meanwhile for the Iranians, Dean says, the stakes are just as great. Their influence -- preserving a Shia-dominated "crescent" from Tehran across Iraq and through Damascus to Beirut hinges on the Assad regime's survival. Some analysts estimate Iran has spent nearly $100 billion in supporting Assad, while hundreds of Iranian militia have been killed fighting for the regime.

The price of a failed deal

So the conflict remains intractable. And for all the failures of the US and Russia to agree a deal, it's the Syrian people who pay the ultimate cost.

Ten million Syrians have been driven from their homes, nearly half of whom have fled the country, 400,000 have been killed, countless thousands detained and tortured. What began with protestors chanting "The people demand the fall of the regime" has become a blood feud in a region where memories are long, Dean says.

According to Aimen Dean, who now works as a consultant on the region for governments and the private sector, tens of thousands of Sunnis living in Aleppo, Idlib, Homs and elsewhere have one question:

"What is it about Assad that the entire Syrian population can go but he can't go?"

In 2011, as street protests in Syria began, Dean forecast that without immediate and forceful international intervention, the civil war would last 10 years and leave a million people dead, sucking in powers around the region and beyond. Fast forward five years and Dean's prognosis still holds up and for now, certainly, the diplomatic cupboard looks very bare.