About the frame, and about doing this kind of design work: When working on designs for things that are very mechanical, and not very aerospacy, I tend to shoot from the hip. I have a pretty healthy aversion to math, and I find solids modelers to be cumbersome. I've grown up building things, so my version of shooting from the hip, in general, is still reasonably accurate with error on the side of overbuilt and heavy.
My approach then is to map out as many known pieces and principles as I can, then try to finagle them around in a basic 3D model till everything is as close to ideal as I can manage. I knew my rails (24.5", 19", and 12.5"), and I already had my motors (3 x 280 oz NEMA23 stepper motors). I made quick models of the rails, screws, ball nuts, and motors so that I could align them the way they would be in the machine. From there I modeled rail blocks and assumed that I would use 1/4" aluminum plate to tie them together.
I went with a "split gantry" layout to keep a high stiffness, meaning only one axis has to be mounted on top of another axis.
This whole process leaves everything floating in space, but with all the parts just where they need to end up in the final machine. Therefore all that needed to be done was to model a steel frame around it for everything to attach to, and take measurements...
Strange as it may be, I do all my non-FEA engineering in Maya3d. It's just quicker to mock things up. It also makes it very easy to rig up motion and limits on things so that I can check for interferences and spacing. The machine is designed for stiffness, not efficient use of the rails. As a result the total motion area is 12x12x6 inches.