How to fill out IFR flight plan for manned helium balloon flight into class A airspace with no predetermined route or destination and less crew?
I just helped a University launch of an unmanned balloon and I used an E-6B for completing the NOTAM for the launch.  GPS and tracking showed that the estimated path deviated from actual path by small numbers. 

We were advised that no IFR FP was required for a small (~3kg payload) unmanned balloon, so none was filed.  We did advise center at launch, and with updates on the way up and down.

Addendum #1
After thinking about this, there are really two parts to this question. The part about route prediction I have addressed in part.  Keep in mind that gliders file IFR and they have little ability to climb higher on demand. The FP can provide an area, just like an IFR FP or and IFR clearance for aircraft can have block airspace, or even routing at pilot's discretion.

The other issue is whether a FP is needed. For manned balloons in controlled airspace, operating under IFR, the answer is clearly yes. But again, there is allot of latitude in what a FP can specify, and what clearance might be issued.

For unmanned balloons, which is where I have more experience, the rules are quite different.  And size is limited.

But again, the FAA can issue waivers, and they are done regularly for all kinds of flights. So just because the rules prohibit or do not allow, doesn't mean that a waiver could be issued to allow.