Here are some photos using O-72 inner/O-81 outer;
Y3 and GGD 21" car. Keep in mind the Y3 is a smaller articulated engine. A Big Boy would hit.
Here are Lionel Centipedes with the 21" cars. They hit.
Here are the Lionel Centipedes with an 18" car. Good to go.
I'm using mostly 4.5" on my layout with O-80 as minimum mainline curve, using various Ross/Atlas/Gargraves curves to keep that distance. I am using flex more.
Even at 4.5" I do not think I can run a Big Boy on the inside track with those 21" cars. However, my transition era PRR long engines can (just barely) including my scale Centipedes, Passenger Shark, T1, Q1/2, and J1. I do not have an S1, and my S2 has not arrived yet, so I don't know about them.
Hope this helps.