Use substitution when the integrand can be factored into something with an "inside function" u and something that's more-or-less the derivative of u (if the constant coefficients don't quite agree, that's ok).
We would use integration by substitution on
because x is a constant multiple of the derivative of x2, which is an inside function:
We can't use substitution on
If we try to let u = x2 it just doesn't work, because we have an extra factor of x hanging around: